Anti-PEG Antibodies Boosted in Humans by SARS-CoV-2 Lipid Nanoparticle mRNA Vaccine

Ju, Yi; Lee, Wen Shi; Pilkington, Emily H.; Kelly, Hannah G.; Li, Shiyao; Selva, Kevin J; Wragg, Kathleen M.; Subbarao, Kanta; Nguyen, Thi H O; Rowntree, Louise C; Allen, Lilith F; Bond, Katherine A.; Williamson, Deborah A; Truong, Nghia P; Plebanski, Magdalena; Kedzierska, Katherine; Mahanty, Siddhartha; Chung, Amy W.; Caruso, Frank; Wheatley, Adam K.; Juno, Jennifer A; Kent, Stephen J.

doi:10.1021/acsnano.2c04543

ScienceOpen: research and publishing network

For Publishers

For Researchers

Blog
About

Search
Advanced search

views

recommends

Record: found
Abstract: found
Article: not found

Anti-PEG Antibodies Boosted in Humans by SARS-CoV-2 Lipid Nanoparticle mRNA Vaccine

research-article

Author(s): Yi Ju ^† ^, ^‡ ^, ^§ ^, , Wen Shi Lee ^† , Emily H. Pilkington ^† ^, ^∥ , Hannah G. Kelly ^† , Shiyao Li ^§ , Kevin J. Selva ^† , Kathleen M. Wragg ^† , Kanta Subbarao ^† ^, ^⊥ , Thi H. O. Nguyen ^† , Louise C. Rowntree ^† , Lilith F. Allen ^† , Katherine Bond ^# , Deborah A. Williamson ^† ^, ^# , Nghia P. Truong ^† ^, ^∥ , Magdalena Plebanski ^‡ , Katherine Kedzierska ^† , Siddhartha Mahanty ⁷ , Amy W. Chung ^† , Frank Caruso ^§ , Adam K. Wheatley ^† , Jennifer A. Juno ^† , Stephen J. Kent ^† ^, ⁸ ^,

Publication date (Electronic): 27 June 2022

Journal: ACS Nano

Publisher: American Chemical Society

Keywords: PEGylated lipid nanoparticle, COVID-19, immunoglobulins, biomolecular coronas, human blood assay, particle−immune cell interactions

Read this article at

ScienceOpenPublisher PMC

Bookmark

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Humans commonly have low level antibodies to poly(ethylene) glycol (PEG) due to environmental exposure. Lipid nanoparticle (LNP) mRNA vaccines for SARS-CoV-2 contain small amounts of PEG, but it is not known whether PEG antibodies are enhanced by vaccination and what their impact is on particle–immune cell interactions in human blood. We studied plasma from 130 adults receiving either the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) mRNA vaccines or no SARS-CoV-2 vaccine for PEG-specific antibodies. Anti-PEG IgG was commonly detected prior to vaccination and was significantly boosted a mean of 13.1-fold (range 1.0–70.9) following mRNA-1273 vaccination and a mean of 1.78-fold (range 0.68–16.6) following BNT162b2 vaccination. Anti-PEG IgM increased 68.5-fold (range 0.9–377.1) and 2.64-fold (0.76–12.84) following mRNA-1273 and BNT162b2 vaccination, respectively. The rise in PEG-specific antibodies following mRNA-1273 vaccination was associated with a significant increase in the association of clinically relevant PEGylated LNPs with blood phagocytes ex vivo. PEG antibodies did not impact the SARS-CoV-2 specific neutralizing antibody response to vaccination. However, the elevated levels of vaccine-induced anti-PEG antibodies correlated with increased systemic reactogenicity following two doses of vaccination. We conclude that PEG-specific antibodies can be boosted by LNP mRNA vaccination and that the rise in PEG-specific antibodies is associated with systemic reactogenicity and an increase of PEG particle–leukocyte association in human blood. The longer-term clinical impact of the increase in PEG-specific antibodies induced by lipid nanoparticle mRNA vaccines should be monitored. It may be useful to identify suitable alternatives to PEG for developing next-generation LNP vaccines to overcome PEG immunogenicity in the future.

Related collections

Most cited references 41

Record: found
Abstract: found
Article: not found

Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

David Khoury, Deborah Cromer, Arnold Reynaldi … (2021)

Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4-28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7-13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic.

0 comments Cited 1905 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Doxil®--the first FDA-approved nano-drug: lessons learned.

Yechezkel Barenholz (2012)

Doxil®, the first FDA-approved nano-drug (1995), is based on three unrelated principles: (i) prolonged drug circulation time and avoidance of the RES due to the use of PEGylated nano-liposomes; (ii) high and stable remote loading of doxorubicin driven by a transmembrane ammonium sulfate gradient, which also allows for drug release at the tumor; and (iii) having the liposome lipid bilayer in a "liquid ordered" phase composed of the high-T(m) (53 °C) phosphatidylcholine, and cholesterol. Due to the EPR effect, Doxil is "passively targeted" to tumors and its doxorubicin is released and becomes available to tumor cells by as yet unknown means. This review summarizes historical and scientific perspectives of Doxil development and lessons learned from its development and 20 years of its use. It demonstrates the obligatory need for applying an understanding of the cross talk between physicochemical, nano-technological, and biological principles. However, in spite of the large reward, ~2 years after Doxil-related patents expired, there is still no FDA-approved generic "Doxil" available. Copyright © 2012 Elsevier B.V. All rights reserved.

0 comments Cited 715 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel

Yinon Bar-On, Yair Goldberg, Micha Mandel … (2021)

Background On July 30, 2021, the administration of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer–BioNTech) was approved in Israel for persons who were 60 years of age or older and who had received a second dose of vaccine at least 5 months earlier. Data are needed regarding the effect of the booster dose on the rate of confirmed coronavirus 2019 disease (Covid-19) and the rate of severe illness. Methods We extracted data for the period from July 30 through August 31, 2021, from the Israeli Ministry of Health database regarding 1,137,804 persons who were 60 years of age or older and had been fully vaccinated (i.e., had received two doses of BNT162b2) at least 5 months earlier. In the primary analysis, we compared the rate of confirmed Covid-19 and the rate of severe illness between those who had received a booster injection at least 12 days earlier (booster group) and those who had not received a booster injection (nonbooster group). In a secondary analysis, we evaluated the rate of infection 4 to 6 days after the booster dose as compared with the rate at least 12 days after the booster. In all the analyses, we used Poisson regression after adjusting for possible confounding factors. Results At least 12 days after the booster dose, the rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of 11.3 (95% confidence interval [CI], 10.4 to 12.3); the rate of severe illness was lower by a factor of 19.5 (95% CI, 12.9 to 29.5). In a secondary analysis, the rate of confirmed infection at least 12 days after vaccination was lower than the rate after 4 to 6 days by a factor of 5.4 (95% CI, 4.8 to 6.1). Conclusions In this study involving participants who were 60 years of age or older and had received two doses of the BNT162b2 vaccine at least 5 months earlier, we found that the rates of confirmed Covid-19 and severe illness were substantially lower among those who received a booster (third) dose of the BNT162b2 vaccine.

0 comments Cited 614 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): ACS Nano

Journal ID (iso-abbrev): ACS Nano

Journal ID (publisher-id): nn

Journal ID (coden): ancac3

Title: ACS Nano

Publisher: American Chemical Society

ISSN (Print): 1936-0851

ISSN (Electronic): 1936-086X

Publication date (Electronic): 27 June 2022

Electronic Location Identifier: acsnano.2c04543

Affiliations

[† ]Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne , Melbourne, VIC 3000, Australia

[‡ ]School of Health and Biomedical Sciences, RMIT University , Bundoora, VIC 3083, Australia

[§ ]Department of Chemical Engineering, The University of Melbourne , Melbourne, VIC 3000, Australia

[∥ ]Department of Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University , Melbourne, VIC 3000, Australia

[⊥ ]WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity , Melbourne, VIC 3000, Australia

[# ]Department of Microbiology, Royal Melbourne Hospital , Melbourne, VIC 3000, Australia

[7 ]Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne , Melbourne, VIC 3000, Australia

[8 ]Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University , Melbourne, VIC 3000, Australia

Author notes

[* ]Email: david.ju@ 123456rmit.edu.au .

[* ]Email: skent@ 123456unimelb.edu.au .

Author information

Yi Ju https://orcid.org/0000-0003-0103-1207

Wen Shi Lee https://orcid.org/0000-0001-7285-4054

Frank Caruso https://orcid.org/0000-0002-0197-497X

Stephen J. Kent https://orcid.org/0000-0002-8539-4891

Article

DOI: 10.1021/acsnano.2c04543

PMC ID: 9261834

PubMed ID: 35758934

SO-VID: 48c006e7-4316-4428-b1e0-a6e6da85449e

License:

This article is made available via the PMC Open Access Subset for unrestricted RESEARCH re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

History

Date received : 09 May 2022

Date accepted : 21 June 2022

Funding

Funded by: Australian Research Council, doi 10.13039/501100000923;

Award ID: DP200100231

Funded by: RMIT University, doi 10.13039/501100001780;

Award ID: NA

Funded by: Department of Health and Ageing, Australian Government, doi 10.13039/501100001027;

Award ID: 2005544

Funded by: National Health and Medical Research Council, doi 10.13039/501100000925;

Award ID: 1149990

Funded by: Australian Research Council, doi 10.13039/501100000923;

Award ID: DP210103114

Custom metadata

document-id-old-9 nn2c04543

document-id-new-14 nn2c04543

ccc-price

ScienceOpen disciplines: Nanotechnology

Keywords: pegylated lipid nanoparticle,covid-19,immunoglobulins,biomolecular coronas,human blood assay,particle−immune cell interactions

Data availability:

ScienceOpen disciplines: Nanotechnology

Keywords: pegylated lipid nanoparticle, covid-19, immunoglobulins, biomolecular coronas, human blood assay, particle−immune cell interactions

Anti-PEG Antibodies Boosted in Humans by SARS-CoV-2 Lipid Nanoparticle mRNA Vaccine

Read this article at

Abstract

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 41

Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

Doxil®--the first FDA-approved nano-drug: lessons learned.

Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 236

Cited by 57

Most referenced authors 860